POLG mutations cause decreased mitochondrial DNA repopulation rates following induced depletion in human fibroblasts

Biochimica et Biophysica Acta - Molecular Basis of Disease

Volumn 1812, Issue 3, 2011, Pages 321-325

  Stewart, Joanna D ^a   Schoeler, Susanne ^b   Sitarz, Kamil S ^a   Horvath, Rita ^a   Hallmann, Kerstin ^b   Pyle, Angela ^a   Yu Wai Man, Patrick ^a   Taylor, Robert W ^a   Samuels, David C ^c   Kunz, Wolfram S ^b   Chinnery, Patrick F ^a  

^a NEWCASTLE UNIVERSITY   (United Kingdom)

^b UNIVERSITY OF BONN   (Germany)

^c VANDERBILT UNIVERSITY MEDICAL CENTER   (United States)

Author keywords

Depletion; Ethidium bromide; Mitochondria; Mitochondrial DNA

Indexed keywords

DNA POLYMERASE; ETHIDIUM BROMIDE; MITOCHONDRIAL DNA; POLG PROTEIN; UNCLASSIFIED DRUG;

ADULT; ALLELE; ARTICLE; CLINICAL ARTICLE; CONTROLLED STUDY; COPY NUMBER VARIATION; FEMALE; FIBROBLAST; GENE MUTATION; HETEROZYGOTE; HUMAN; HUMAN CELL; MALE; MITOCHONDRIAL DNA DEPLETION; MITOCHONDRIAL DNA REPLICATION; NEWBORN; PRIORITY JOURNAL;

ADULT; AMINO ACID SUBSTITUTION; CASE-CONTROL STUDIES; DIFFUSE CEREBRAL SCLEROSIS OF SCHILDER; DNA REPLICATION; DNA, MITOCHONDRIAL; DNA-DIRECTED DNA POLYMERASE; ENZYME INHIBITORS; EPILEPSY; ETHIDIUM; FEMALE; FIBROBLASTS; HETEROZYGOTE; HOMOZYGOTE; HUMANS; INFANT; MALE; MITOCHONDRIA; MUSCULAR DISEASES; MUTATION; THYMIDINE KINASE;

EID: 78650786456     PISSN: 09254439     EISSN: None     Source Type: Journal    
DOI: 10.1016/j.bbadis.2010.11.012     Document Type: Article

References (32)

1. Birky C.W. Relaxed and stringent genomes: why cytoplasmic genes don't obey Mendel's laws. J. Hered. 1994, 85:355-365.
2. Copeland W.C. Inherited mitochondrial diseases of DNA replication. Annu. Rev. Med. 2008, 59:131-146.
3. Van Goethem G., Dermaut B., Lofgren A., Martin J.-J., Van Broeckhoven C. Mutation of POLG is associated with progressive external ophthalmoplegia characterized by mtDNA deletions. Nat. Genet. 2001, 28:211-212.
4. Longley M.J., Clark S., Yu Wai Man C., Hudson G., Durham S.E., Taylor R.W., Nightingale S., Turnbull D.M., Copeland W.C., Chinnery P.F. Mutant POLG2 disrupts DNA polymerase gamma subunits and causes progressive external ophthalmoplegia. Am. J. Hum. Genet. 2006, 78:1026-1034.
5. Spelbrink J.N., Li F.Y., Tiranti V., Nikali K., Yuan Q.P., Wanrooij S., Garrido N., Comi G.P., Morandi L., Santoro L., Toscano A., Fabrizi G.M., Somer H., Croxen R., Beeson D., Poulton J., Suomalainen A., Jacobs H.T., Zeviani M., Larsson C. Human mitochondrial DNA deletions associated with mutations in the gene encoding Twinkle, a phage T7 gene 4-like protein localised in mitochondria. Nat. Genet. 2001, 28:223-231.
6. Kaukonen J., Juselius J.K., Tiranti V., Kyttala A., Zeviani M., Comi G.P., Keranen S., Peltonen L., Suomalainen A. Role of adenine nucleotide translocator 1 in mtDNA maintenance. Science 2000, 289:782-785.
7. Hudson G., Amati-Bonneau P., Blakely E.L., Stewart J.D., He L., Schaefer A.M., Griffiths P.G., Ahlqvist K., Suomalainen A., Reynier P., McFarland R., Turnbull D.M., Chinnery P.F., Taylor R.W. Mutation of OPA1 causes dominant optic atrophy with external ophthalmoplegia, ataxia, deafness and multiple mitochondrial DNA deletions: a novel disorder of mtDNA maintenance. Brain 2007, 131:329-337.
8. Graziewicz M.A., Longley M.J., Copeland W.C. DNA polymerase gamma in mitochondrial DNA replication and repair. Chem. Rev. 2006, 106:383-405.
9. Schon E.A., Bonilla E., DiMauro S. Mitochondrial DNA mutations and pathogenesis. J. Bioenerg. Biomembr. 1997, 29:131-149.
10. Taylor R.W., Turnbull D.M. Mitochondrial DNA mutations in human disease. Nat. Rev. Genet. 2005, 6:389-402.
11. Naviaux R.K., Nguyen K.V. POLG mutations associated with Alpers' syndrome and mitochondrial DNA depletion. Ann. Neurol. 2004, 55:706-712.
12. Hakonen A.H., Isohanni P., Paetau A., Herva R., Suomalainen A., Lonnqvist T. Recessive Twinkle mutations in early onset encephalopathy with mtDNA depletion. Brain 2007, 130:3032-3040.
13. Saada A., Shaag A., Mandel H., Nevo Y., Eriksson S., Elpeleg O. Mutant mitochondrial thymidine kinase in mitochondrial DNA depletion myopathy. Nat. Genet. 2001, 29:342-344.
14. Zeviani M., Di Donato S. Mitochondrial disorders. Brain 2004, 127:2153-2172.
15. Wanrooij S., Goffart S., Pohjoismaki J.L., Yasukawa T., Spelbrink J.N. Expression of catalytic mutants of the mtDNA helicase Twinkle and polymerase POLG causes distinct replication stalling phenotypes. Nucleic Acids Res. 2007, 35:3238-3251.
16. Taanman J.W., Rahman S., Pagnamenta A.T., Morris A.A., Bitner-Glindzicz M., Wolf N.I., Leonard J.V., Clayton P.T., Schapira A.H. Analysis of mutant DNA polymerase gamma in patients with mitochondrial DNA depletion. Hum. Mutat. 2009, 30:248-254.
17. Leibowitz R.D. The effect of ethidium bromide on mitochondrial DNA synthesis and mitochondrial DNA structure in HeLa cells. J. Cell Biol. 1971, 51:116-122.
18. Seidel-Rogol B.L., Shadel G.S. Modulation of mitochondrial transcription in response to mtDNA depletion and repletion in HeLa cells. Nucleic Acids Res. 2002, 30:1929-1934.
19. King M.P., Attardi G. Isolation of human cell lines lacking mitochondrial DNA. Methods Enzymol. 1996, 264:304-313.
20. King M.P., Attardi G. Human cells lacking mtDNA: repopulation with exogenous mitochondria by complementation. Science 1989, 246:500-503.
21. Moraes C.T., Kenyon L., Hao H. Mechanisms of human mitochondrial DNA maintenance: the determining role of primary sequence and length over function. Mol. Biol. Cell 1999, 10:3345-3356.
22. Diaz F., Bayona-Bafaluy M.P., Rana M., Mora M., Hao H., Moraes C.T. Human mitochondrial DNA with large deletions repopulates organelles faster than full-length genomes under relaxed copy number control. Nucleic Acids Res. 2002, 30:4626-4633.
23. Horvath R., Hudson G., Ferrari G., Fütterer N., Ahola S., Lamantea E., Prokisch H., Lochmüller H., McFarland R., Ramesh V., Klopstock T., Freisinger P., Salvi F., Mayr J.A., Santer R., Tesarova M., Zeman J., Udd B., Taylor R.W., Turnbull D., Hanna M., Fialho D., Suomalainen A., Zeviani M., Chinnery P.F. Phenotypic spectrum associated with mutations of the mitochondrial polymerase gamma gene. Brain 2006, 129:1674-1684.
24. Zsurka G., Baron M., Stewart J.D., Kornblum C., Bos M., Sassen R., Taylor R.W., Elger C.E., Chinnery P.F., Kunz W.S. Clonally expanded mitochondrial DNA mutations in epileptic individuals with mutated DNA polymerase gamma. J. Neuropathol. Exp. Neurol. 2008, 67:857-866.
25. Durham S.E., Bonilla E., Samuels D.C., DiMauro S., Chinnery P.F. Mitochondrial DNA copy number threshold in mtDNA depletion myopathy. Neurology 2005, 65:453-455.
26. Durham S.E., Brown D.T., Turnbull D.M., Chinnery P.F. Progressive depletion of mtDNA in mitochondrial myopathy. Neurology 2006, 67:502-504.
27. Kraytsberg Y., Khrapko K. Single-molecule PCR: an artifact-free PCR approach for the analysis of somatic mutations. Expert Rev. Mol. Diagn. 2005, 5:809-815.
28. Ashley N., O'Rourke A., Smith C., Adams S., Gowda V., Zeviani M., Brown G.K., Fratter C., Poulton J. Depletion of mitochondrial DNA in fibroblast cultures from patients with POLG1 mutations is a consequence of catalytic mutations. Hum. Mol. Genet. 2008, 17:2496-2506.
29. Gross N.J., Getz G.S., Rabinowitz M. Apparent turnover of mitochondrial deoxyribonucleic acid and mitochondrial phospholipids in the tissues of the rat. J. Biol. Chem. 1969, 244:1552-1562.
30. Emmerson C.F., Brown G.K., Poulton J. Synthesis of mitochondrial DNA in permeabilised human cultured cells. Nucleic Acids Res. 2001, 29:E1.
31. Taanman J.W., Muddle J.R., Muntau A.C. Mitochondrial DNA depletion can be prevented by dGMP and dAMP supplementation in a resting culture of deoxyguanosine kinase-deficient fibroblasts. Hum. Mol. Genet. 2003, 12:1839-1845.
32. Frangini M., Rampazzo C., Franzolin E., Lara M.C., Vila M.R., Marti R., Bianchi V. Unchanged thymidine triphosphate pools and thymidine metabolism in two lines of thymidine kinase 2-mutated fibroblasts. FEBS J. 2009, 276:1104-1113.